Treatment and outcomes of patients with gastrointestinal toxicity following immunotherapy: A large multi-center retrospective study in the United Kingdom by the National Oncology Trainees Collaborative for Healthcare Research (NOTCH) (2022)

Type of publication:
Conference abstract

Author(s):
Swaminathan M.; Angelakas A.; Baxter M.; Cotton J.; Dobeson C.B.; Feeney L.; Gault A.C.; Hughes D.J.; Jones C.; Lee R.; Mughal S.A.; *Parikh S.P.; Pritchard M.; Rodgers L.J.; Rowe M.P.; Salawu A.T.; Shotton R.; Tinsley N.; Tivey A.; Olsson-Brown A.C.;

Citation:
Immuno-Oncology and Technology. Conference: ESMO Immuno-Oncology Congress 2022. Geneva Switzerland. 16(Supplement 1) (no pagination), 2022. Article Number: 100230. Date of Publication: December 2022.

Abstract:
Background: Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of many cancers, but their use has been associated with the development of gastrointestinal (GI) toxicities such as colitis and hepatitis. Method(s): A multi-center retrospective study across 12 National Health Service centers across the United Kingdom (UK) was conducted by the UK National Oncology Trainees Collaborative for Healthcare Research (NOTCH) over a 2-year period. The study included patients receiving ICIs for malignant melanoma, non-small lung cancer and renal cell cancer as standard of care. Occurrence of clinically significant (>=grade 2) GI toxicity was assessed and correlated with subsequent treatment and outcomes. Multiple logistic regression was used to assess correlation. For overall survival (OS), Kaplan-Meier and log-rank tests were utilised. Result(s): The cohort included 2049 patients. 1230 (60%) were male with a median age of 66. Colitis occurred in 182 (8.9%) patients and hepatitis in 129 (6.3%). Of the patients where treatment was recorded, 129 (70.9%) received treatment with systemic steroids alone and 37 (20.3%) required second-line immunosuppressants (IS) in the colitis group. In the hepatitis group, 101 (78.3%) had steroids alone with 19 (14.7%) having IS. Improved OS was found in patients who experienced colitis (HR 2.59 95%CI: 2.15 to 3.11, p<0.0001) and hepatitis (HR 2.26, 95%CI: 1.84 to 2.79, p=<0.0001) compared to those with no adverse events. Pre-existing autoimmune disease (p=0.02) and combination ICIs (p=0.006) were predictors of colitis that required IS whilst grade 2 and 3 hepatitis (p<0.001) were predictors of hepatitis needing IS. The use of IS did not affect OS significantly in the colitis group (p=0.372) but did correlate with survival in the hepatitis group (p=0.037). Patients that were able to continue treatment with ICIs after toxicity had an increased OS in both groups (p<0.001). Conclusion(s): Patients with GI toxicity following treatment with ICIs have improved OS. The use of IS did not significantly affect OS which suggests they should continue to be utilised in the treatment of GI toxicity. Legal entity responsible for the study: United Kingdom National Oncology Trainees Collaborative for Healthcare Research (NOTCH).

Link to full-text [no password required]

Craniofacial Osteosarcoma: A case report. (2022)

Type of publication:
Conference abstract

Author(s):
*Venkatasami M.; *Harrison K.;

Citation:
British Journal of Oral and Maxillofacial Surgery. Conference: BAOMS Annual Scientific Meeting. London United Kingdom. 60(10) (pp e63), 2022. Date of Publication: December 2022.

Abstract:
Introduction/Aims: Osteosarcoma is the most common primary bone tumour, with 10% of cases affecting the head and neck. Osteosarcoma occurs later in life, usually, in the 4-5th decade with a male predilection and predominantly affects the mandible; the maxilla being the second-most affected site. Prognosis is strongly dependent on negative resection margins and neoadjuvant chemo-radiotherapy in select cases. Case Description: A 58 year-old male, non-smoker, presented with a lump in his left upper jaw which occasionally bled and got caught during mastication. Previous medical history included quiescent relapsing-remitting multiple sclerosis and absent seizures. Clinical examination revealed a suspicious exophytic mass in the upper left tuberosity of the maxilla with no associated lymphadenopathy. <br/>Finding(s): Radiological investigations revealed a metabolically active left maxillary lesion with maxillary sinus destruction, representing primary malignancy with no nodal disease. Histological analysis of a punch biopsy revealed a fibrosseous lesion, referred to a sarcoma centre for interpretation. Immunohistochemistry showed AE1/AE3 and CK(MNF.116) positivity in occasional cells with a ki67 proliferation index of 60%. This was diagnostic of grade-2-3 osteosarcoma. Multidisciplinary management included neoadjuvant chemotherapy prior to total maxillectomy and dental prosthetic rehabilitation. Patient is still under follow-up. Conclusions/Clinical Relevance: This case of primary osteosarcoma of the maxilla is rare and scarcely reported in literature. Upon clinical appearance, this exophytic lesion could resemble squamous cell carcinoma, thus it is important to consider differential diagnoses, including osteosarcoma, which requires prompt and early specialist intervention to maximise the chances of negative surgical margins, which is the mainstay of treatment for disease prognosis.

Bariatric surgeons' experiences of working in the first year of the pandemic (2022)

Type of publication:
Journal article

Author(s):
Graham Y.N.H.; Mahawar K.; Singhal R.; Madhok B.; Yang W.; *Riera M.; Martinez-Duartez P.; Pouwels S.; Sharma M.; Hayes C.

Citation:
Obesity Science and Practice. (no pagination), 2022. Date of Publication: 2022 [epub ahead of print]

Abstract:
Background: The first year of the Covid-19 pandemic saw drastic changes to bariatric surgical practice, including postponement of procedures, altered patient care and impacting on the role of bariatric surgeons. The consequences of this both personally and professionally amongst bariatric surgeons has not as yet been explored. Aim(s): The aim of this research was to understand bariatric surgeons' perspectives of working during the first year of the pandemic to explore the self-reported personal and professional impact. Method(s): Using a retrospective, two phased, study design with global participants recruited from closed, bariatric surgical units. The first phase used a qualitative thematic analytic framework to identify salient areas of importance to surgeons. Themes informed the construction of an on-line, confidential survey to test the potential generalizability of the interview findings with a larger representative population from the global bariatric surgical community. Finding(s): Findings of the study revealed that the first year of the pandemic had a detrimental effect on bariatric surgeons both personally and professionally globally. Conclusion(s): This study has identified the need to build resilience of bariatric surgeons so that the practice of self-care and the encouragement of help-seeking behaviors can potentially be normalized, which will in turn increase levels of mental health and wellbeing.

Link to full-text [open access - no password required]

Global Level of Harm experienced by Bariatric Surgeons for Bariatrics surgical interventions: An exploration of predictors (2022)

Type of publication:
Conference abstract

Author(s):
Cheruvu C.; Bangash A.H.; Isik A.; Parmar C.; Galanis M.; Yang W.; Kok J.H.H.; *Bandyopadhyay S.K.; Di Maggio F.; Atici S.D.; Abouelazayem M.; Viswanath Y.K.S.

Citation:
British Journal of Surgery. Conference: AUGIS Annual Scientific Meeting. Aberdeen United Kingdom. 109(Supplement 9) (pp ix17-ix18), 2022. Date of Publication: December 2022.

Abstract:
Background: COVID-19 pandemic has taken the world by surprise with the depth and breadth of its effect on all walks of life, bariatric surgery being no exception. With the scientific literature hitherto unable to comment and ascertain the influence of the COVID-19 pandemic on bariatric surgery and the level of harm experienced by bariatric surgeons, we- TUGS 'Level of Harm' collaborative group- attempted to gauge the effect of the said pandemic on bariatrics surgery specifically vis a vis the level of harm experienced by bariatric surgeons due to the pandemic. Method(s): A virtual questionnaire- developed on both: Google forms and Survey Monkey- was circulated via TUGS social media platforms to reach bariatric consultant surgeons, fellows and residents practising throughout the world in a bid to explore the influence of the COVID-19 pandemic on their surgical practice including but not limited to the annual surgical volume including re-do surgeries volume and postoperative complications. Moreover, they were also requested to categorise their respective level of harm vis a vis bariatric surgical interventions they undertake. After de-identification of the data, SPSS (V.26) was adopted to undergo statistical analysis. After exploring the dataset by descriptive analyses, the Chi-square test was applied to pursue the association of categorical variables with the reported level of harm. A double-sided p-value of less than 0.05 was considered statistically significant. Result(s): 16.8% of the respondents (21/125) indicated no harm vis a vis bariatrics surgery work whereas a comparative 18.4% of the respondents (23/125) reported moderate harm with significant worsening of symptoms. None of those who indicated less than 10% increase in surgery waitlisted patients being subjected to endoscopic interventions (0/14) reported Moderate Harm for bariatrics surgery work with significant worsening of symptoms whereas 1 in every 3 of those who indicated between 10% to 25% increase in surgery waitlisted patients being subjected to endoscopic interventions (5/15) reported such level of harm for bariatrics surgery work. (p < 0.001) Upon exhaustive sub-group analysis, it was uncovered that 33.6% of bariatrics surgical professionals perceived no harm (no evidence of change in clinical condition) during gastric band or related surgery work with only 4% perceiving Moderate Harm (significant worsening of symptoms/ comorbidities control/ minor increase in medications) for such surgical interventions. All of those who reported No harm for gastric band or related surgical work reported that Single anastomosis duodeno-ileal bypass (SADI-S) accounts for 10% of their practice whereas none of those who indicated that SADI-S accounts for more than 10% of their practice reported No harm for such surgical work. (p = 0.019) Conclusion(s): The global snapshot illustrates a trend of low harm vis a vis bariatrics surgery work in surgical professionals practising in the private sector with a lesser number of patients developing COVID-19 postoperatively and no postoperative COVID-19 related mortality. The patient being subjected to endoscopic intervention portends a higher level of harm for bariatrics surgical work- strict adherence to criteria and safety protocols being a logical inference. For gastric band and related surgery work, preoperative COVID-19 testing appears to be influenced by confounders in its effect on the surgeon's level of harm for the said interventions warranting further exploration. SADI-S, at a cut-off of 10%, exhibits strong interaction with the surgeon's level of harm for gastric band insertion and relation surgery work. Women surgical professionals came out to exhibit equivalent mental resilience and technical prowess at par with their male colleagues when it came to bariatrics surgical intervention

Link to full-text [no password required]

Folliculitis decalvans managed with long pulsed Nd:YAG; our experience and a review of the literature (2022)

Type of publication:
Conference abstract

Author(s):
*Oh S.; *Badrol S.; *Tzortzis S.; El Shimy N.; Murdoch S.;

Citation:
Lasers in Medical Science. Conference: British Medical Laser Association Annual Conference, BMLA 2022. Edinburgh United Kingdom. 37(9) (pp 3769), 2022. Date of Publication: December 2022.

Abstract:
Background Folliculitis decalvans (FD) is a rare inflammatory disorder predominantly of the scalp that can progress to cicatrical alopecia. Mainstay treatment is antibiotics; however, resolution is difficult, and relapse is common. Only three cases of FD treated with neodymium:yttrium aluminum garnet (Nd:YAG) laser exist in the literature. We present two cases of recalcitrant FD managed with long pulsed Nd:YAG laser and a literature review. Study Design Retrospective case series of two patients with FD treated with long pulsed Nd:YAG laser. Results The first case was a 49-year-old male with Fitzpatrick skin type II. Previous unsuccessful treatment included oral doxycycline and isotretinoin. A course of eight sessions of Nd:YAG laser (CynergyTM, Cynosure) was performed with settings of 50J/cm<inf>2</inf>, 20msec pulse duration, and 10mm spot size. Complete resolution of FD was achieved and remained stable without adjuvant treatment at 6 months post laser. The second case was a 46-year-old male with Fitzpatrick skin type IV with 9-years history of FD. Previously, oral antibiotics (clindamycin, rifampicin, erythromycin, ciprofloxacin) as well as dapsone, intralesional triamcinolone and acitretin treatment was trialled without success. A total of four successful treatments with Nd:YAG laser was completed with settings of 30J/cm<inf>2</inf>, 40msec pulse duration, and 15mm spot size. Treatment is ongoing. Conclusion Our experience of Nd:YAG laser treatment of FD have been positive. All cases from literature report full resolution of FD maintained without adjuvant treatment between 6 months to 1.5 years after final treatment. Treatment with Nd:YAG laser is an option for patients suffering from recalcitrant FD.

Link to full-text [no password required]

Whole-genome sequencing reveals host factors underlying critical COVID-19 (2022)

Type of publication:
Journal article

Author(s):
Kousathanas A.; Pairo-Castineira E.; Rawlik K.; Stuckey A.; Odhams C.A.; Russell C.D.; Malinauskas T.; Wu Y.; Shen X.; Elliott K.S.; Griffiths F.; Oosthuyzen W.; Morrice K.; Keating S.; Wang B.; Rhodes D.; Klaric L.; Zechner M.; Parkinson N.; Siddiq A.; Goddard P.; Donovan S.; Maslove D.; Nichol A.; Semple M.G.; Zainy T.; Maleady-Crowe F.; Todd L.; Salehi S.; Knight J.; Elgar G.; Chan G.; Arumugam P.; Patch C.; Rendon A.; Bentley D.; Kingsley C.; Kosmicki J.A.; Horowitz J.E.; Baras A.; Abecasis G.R.; Ferreira M.A.R.; Justice A.; Mirshahi T.; Oetjens M.; Rader D.J.; Ritchie M.D.; Verma A.; Fowler T.A.; Shankar-Hari M.; Summers C.; Hinds C.; Horby P.; McAuley D.; Montgomery H.; Openshaw P.J.M.; Elliott P.; Walsh T.; Tenesa A.; Fawkes A.; Rowan K.; Ponting C.P.; Vitart V.; Wilson J.F.; Yang J.; Bretherick A.D.; Scott R.H.; Hendry S.C.; Moutsianas L.; Law A.; Caulfield M.J.; Baillie J.K.; Begg C.; Ling L.; Millar J.; Pereira A.C.; Aravindan L.; Armstrong R.; Biggs H.; Boz C.; Clark R.; Coutts A.; Coyle J.; Cullum L.; Das S.; Day N.; Donnelly L.; Finernan P.; Fourman M.H.; Furlong A.; Furniss J.; Gallagher B.; Gilchrist T.; Golightly A.; Hafezi K.; Hamilton D.; Hendry R.; Law D.; Law R.; Law S.; Lidstone-Scott R.; Macgillivray L.; Maclean A.; Mal H.; McCafferty S.; McMaster E.; Meikle J.; Moore S.C.; Murphy S.; Hellen M.; Zheng C.; Chen J.; Paterson T.; Schon K.; Stenhouse A.; Das M.; Swets M.; Szoor-McElhinney H.; Taneski F.; Turtle L.; Wackett T.; Ward M.; Weaver J.; Wrobel N.; Arbane G.; Bociek A.; Campos S.; Grau N.; Jones T.O.; Lim R.; Marotti M.; Ostermann M.; Whitton C.; Alldis Z.; Astin-Chamberlain R.; Bibi F.; Biddle J.; Blow S.; Bolton M.; Borra C.; Bowles R.; Burton M.; Choudhury Y.; Cox A.; Easthope A.; Ebano P.; Fotiadis S.; Gurasashvili J.; Halls R.; Hartridge P.; Kallon D.; Kassam J.; Lancoma-Malcolm I.; Matharu M.; May P.; Mitchelmore O.; Newman T.; Patel M.; Pheby J.; Pinzuti I.; Prime Z.; Prysyazhna O.; Shiel J.; Tierney C.; Wood S.; Zak A.; Zongo O.; Bonner S.; Hugill K.; Liggett S.; Headlam E.; Bandla N.; Gellamucho M.; Davies M.; Thompson C.; Abdelrazik M.; Bakthavatsalam D.; Elhassan M.; Ganesan A.; Haldeos A.; Moreno-Cuesta J.; Purohit D.; Vincent R.; Xavier K.; Frater A.; Saleem M.; Carter D.; Lamond Z.; Wall A.; Fernandez-Roman J.; Hamilton D.O.; Johnson E.; Johnston B.; Martinez M.L.; Mulla S.; Shaw D.; Waite A.A.C.; Waugh V.; Welters I.D.; Williams K.; Cavazza A.; Cockrell M.; Corcoran E.; Depante M.; Finney C.; Jerome E.; McPhail M.; Nayak M.; Noble H.; O'Reilly K.; Pappa E.; Saha S.; Knighton A.; Antcliffe D.; Banach D.; Brett S.; Coghlan P.; Fernandez Z.; Gordon A.; Rojo R.; Arias S.S.; Templeton M.; Meredith M.; Morris L.; Ryan L.; Clark A.; Sampson J.; Peters C.; Dent M.; Langley M.; Ashraf S.; Wei S.; Andrew A.; Bashyal A.; Davidson N.; Hutton P.; McKechnie S.; Wilson J.; Baptista D.; Crowe R.; Fernandes R.; Herdman-Grant R.; Joseph A.; O'Connor D.; Allen M.; Loveridge A.; McKenley I.; Morino E.; Naranjo A.; Simms R.; Sollesta K.; Swain A.; Venkatesh H.; Khera J.; Fox J.; Andrew G.; Barclay L.; Callaghan M.; Campbell R.; Clark S.; Hope D.; Marshall L.; McCulloch C.; Briton K.; Singleton J.; Birch S.; Brimfield L.; Daly Z.; Pogson D.; Rose S.; Nown A.; Battle C.; Brinkworth E.; Harford R.; Murphy C.; Newey L.; Rees T.; Williams M.; Arnold S.; Polgarova P.; Stroud K.; Meaney E.; Jones M.; Ng A.; Agrawal S.; Pathan N.; White D.; Daubney E.; Elston K.; Grauslyte L.; Hussain M.; Phull M.; Pogreban T.; Rosaroso L.; Salciute E.; Franke G.; Wong J.; George A.; de Gordoa L.O.-R.; Peasgood E.; Phillips C.; Bates M.; Dasgin J.; Gill J.; Nilsson A.; Scriven J.; Collins A.; Khaliq W.; Gude E.T.; Delgado C.C.; Dawson D.; Ding L.; Durrant G.; Ezeobu O.; Farnell-Ward S.; Kanu R.; Leaver S.; Maccacari E.; Manna S.; Saluzzio R.P.; Queiroz J.; Samakomva T.; Sicat C.; Texeira J.; Da Gloria E.F.; Lisboa A.; Rawlins J.; Mathew J.; Kinch A.; Hurt W.J.; Shah N.; Clark V.; Thanasi M.; Yun N.; Patel K.; Bennett S.; Goodwin E.; Jackson M.; Kent A.; Tibke C.; Woodyatt W.; Zaki A.; Abraheem A.; Bamford P.; Cawley K.; Dunmore C.; Faulkner M.; Girach R.; Jeffrey H.; Jones R.; London E.; Nagra I.; Nasir F.; Sainsbury H.; Smedley C.; Patel T.; Smith M.; Chukkambotla S.; Kazi A.; Hartley J.; Dykes J.; Hijazi M.; Keith S.; Khan M.; Ryan-Smith J.; Springle P.; Thomas J.; Truman N.; Saad S.; Coleman D.; Fine C.; Matt R.; Gay B.; Dalziel J.; Ali S.; Goodchild D.; Harling R.; Bhatterjee R.; Goddard W.; Davison C.; Duberly S.; Hargreaves J.; Bolton R.; Davey M.; Golden D.; Seaman R.; Cherian S.; Cutler S.; Heron A.E.; Roynon-Reed A.; Szakmany T.; Williams G.; Richards O.; Cheema Y.; Brooke H.; Buckley S.; Suarez J.C.; Charlesworth R.; Hansson K.; Norris J.; Poole A.; Rose A.; Sandhu R.; Sloan B.; Smithson E.; Thirumaran M.; Wagstaff V.; Metcalfe A.; Brunton M.; Caterson J.; Coles H.; Frise M.; Rai S.G.; Jacques N.; Keating L.; Tilney E.; Bartley S.; Bhuie P.; Gibson S.; Lyle A.; McNeela F.; Radhakrishnan J.; Hughes A.; Yates B.; Reynolds J.; Campbell H.; Thompsom M.; Dodds S.; Duffy S.; Greer S.; Shuker K.; Tridente A.; Khade R.; Sundar A.; Tsinaslanidis G.; Birkinshaw I.; Carter J.; Howard K.; Ingham J.; Joy R.; Pearson H.; Roche S.; Scott Z.; Bancroft H.; Bellamy M.; Carmody M.; Daglish J.; Moore F.; Rhodes J.; Sangombe M.; Kadiri S.; Croft M.; White I.; Frost V.; Aquino M.; Jha R.; Krishnamurthy V.; Lim L.; Combes E.; Joefield T.; Monnery S.; Beech V.; Trotman S.; Christine Almaden-Boyle; Austin P.; Cabrelli L.; Cole S.; Casey M.; Chapman S.; Whyte C.; Baird Y.; Butler A.; Chadbourn I.; Folkes L.; Fox H.; Gardner A.; Gomez R.; Hobden G.; Hodgson L.; King K.; Margarson M.; Martindale T.; Meadows E.; Raynard D.; Thirlwall Y.; Helm D.; Margalef J.; Criste K.; Cusack R.; Golder K.; Golding H.; Jones O.; Leggett S.; Male M.; Marani M.; Prager K.; Williams T.; Roberts B.; Salmon K.; Anderson P.; Archer K.; Austin K.; Davis C.; Durie A.; Kelsall O.; Thrush J.; Vigurs C.; Wild L.; Wood H.-L.; Tranter H.; Harrison A.; Cowley N.; McAlindon M.; Burtenshaw A.; Digby S.; Low E.; Morgan A.; Cother N.; Rankin T.; Clayton S.; McCurdy A.; Ahmed C.; Baines B.; Clamp S.; Colley J.; Haq R.; Hayes A.; Hulme J.; Hussain S.; Joseph S.; Kumar R.; Maqsood Z.; Purewal M.; Benham L.; Bradshaw Z.; Brown J.; Caswell M.; Cupitt J.; Melling S.; Preston S.; Slawson N.; Stoddard E.; Warden S.; Deacon B.; Lynch C.; Pothecary C.; Howe G.S.; Singh J.; Turner K.; Ellis H.; Stroud N.; Dearden J.; Dobson E.; Drummond A.; Mulcahy M.; Munt S.; O'Connor G.; Philbin J.; Rishton C.; Tully R.; Winnard S.; Cathcart S.; Duffy K.; Puxty A.; Puxty K.; Turner L.; Ireland J.; Semple G.; Long K.; Whiteley S.; Wilby E.; Ogg B.; Cowton A.; Kay A.; Kent M.; Potts K.; Wilkinson A.; Campbell S.; Brown E.; Melville J.; Naisbitt J.; Joseph R.; Lazo M.; Walton O.; Neal A.; Alexander P.; Allen S.; Bradley-Potts J.; Brantwood C.; Egan J.; Felton T.; Padden G.; Ward L.; Moss S.; Glasgow S.; Abel L.; Brett M.; Digby B.; Gemmell L.; Hornsby J.; MacGoey P.; O'Neil P.; Price R.; Rodden N.; Rooney K.; Sundaram R.; Thomson N.; Hopkins B.; Thrasyvoulou L.; Willis H.; Coulding M.; Jude E.; McCormick J.; Mercer O.; Potla D.; Rehman H.; Savill H.; Turner V.; Downes C.; Holding K.; Riches K.; Hilton M.; Hayman M.; Subramanian D.; Daniel P.; Adanini O.; Bhatia N.; Msiska M.; Collins R.; Clement I.; Gulati A.; Hays C.; Webster K.; Hudson A.; Webster A.; Stephenson E.; McCormack L.; Slater V.; Nixon R.; Hanson H.; Fearby M.; Kelly S.; Bridgett V.; Robinson P.; Camsooksai J.; Humphrey C.; Jenkins S.; Reschreiter H.; Wadams B.; Death Y.; Bastion V.; Clarke D.; David B.; Kent H.; Lorusso R.; Lubimbi G.; Murdoch S.; Penacerrada M.; Valentine J.; Vochin A.; Wulandari R.; Djeugam B.; Bell G.; English K.; Katary A.; Wilcox L.; Bruce M.; Connolly K.; Duncan T.; Michael H.T.; Lindergard G.; Hey S.; Fox C.; Alfonso J.; Durrans L.J.; Guerin J.; Blackledge B.; Harris J.; Hruska M.; Eltayeb A.; Lamb T.; Hodgkiss T.; Cooper L.; Rothwell J.; Allan A.; Anderson F.; Kaye C.; Liew J.; Medhora J.; Scott T.; Trumper E.; Botello A.; Lankester L.; Nikitas N.; Wells C.; Stowe B.; Spencer K.; Brandwood C.; Smith L.; Kolakaluri L.; Baines D.; Sukumaran A.; Apetri E.; Basikolo C.; Catlow L.; Charles B.; Dark P.; Doonan R.; Harvey A.; Horner D.; Knowles K.; Lee S.; Lomas D.; Lyons C.; Marsden T.; McLaughlan D.; McMorrow L.; Pendlebury J.; Perez J.; Poulaka M.; Proudfoot N.; Slaughter M.; Slevin K.; Thomas V.; Walker D.; Michael A.; Collis M.; Cosier T.; Millen G.; Richardson N.; Schumacher N.; Weston H.; Rand J.; Baxter N.; Henderson S.; Kennedy-Hay S.; Rooney L.; Sim M.; McCreath G.; Akeroyd L.; Bano S.; Bromley M.; Gurr L.; Lawton T.; Morgan J.; Sellick K.; Warren D.; Wilkinson B.; McGowan J.; Ledgard C.; Stacey A.; Pye K.; Bellwood R.; Bentley M.; Bewley J.; Garland Z.; Grimmer L.; Gumbrill B.; Johnson R.; Sweet K.; Webster D.; Efford G.; Convery K.; Fottrell-Gould D.; Hudig L.; Keshet-Price J.; Randell G.; Stammers K.; Bokhari M.; Linnett V.; Lucas R.; McCormick W.; Ritzema J.; Sanderson A.; Wild H.; Rostron A.; Roy A.; Woods L.; Cornell S.; Wakinshaw F.; Rogerson K.; Jarmain J.; Parker R.; Reddy A.; Turner-Bone I.; Harding P.; Abernathy C.; Foster L.; Gratrix A.; Martinson V.; Parkinson P.; Stones E.; Carbral-Ortega L.; Bercades G.; Brealey D.; Hass I.; MacCallum N.; Martir G.; Raith E.; Reyes A.; Smyth D.; Zitter L.; Benyon S.; Marriott S.; Park L.; Keenan S.; Gordon E.; Quinn H.; Baines K.; Cagova L.; Fofano A.; Garner L.; Holcombe H.; Mepham S.; Mitchell A.M.; Mwaura L.; Praman K.; Vuylsteke A.; Zamikula J.; Purewal B.; Rivers V.; Bell S.; Blakemore H.; Borislavova B.; Faulkner B.; Gendall E.; Goff E.; Hayes K.; Thomas M.; Worner R.; Smith K.; Stephens D.; Mew L.; Mwaura E.; Stewart R.; Williams F.; Wren L.; Sutherland S.-B.; Bevan E.; Martin J.; Trodd D.; Watson G.; Brown C.W.; Akinkugbe O.; Bamford A.; Beech E.; Belfield H.; Bell M.; Davies C.; Jones G.A.L.; McHugh T.; Meghari H.; O'Neill L.; Peters M.J.; Ray S.; Tomas A.L.; Burn I.; Hambrook G.; Manso K.; Penn R.; Shanmugasundaram P.; Tebbutt J.; Thornton D.; Davies R.; Duffin D.; Hill H.; Player B.; Thomas E.; Griffin D.; Muchenje N.; Mupudzi M.; Partridge R.; Conyngham J.-A.; Thomas R.; Wright M.; Corral M.A.; Jacob R.; Jones C.; Denmade C.; Beavis S.; Dale K.; Gascoyne R.; Hawes J.; Pritchard K.; Stevenson L.; Whileman A.; Doble P.; Hutter J.; Pawley C.; Shovelton C.; Vaida M.; Butcher D.; O'Sullivan S.; Butterworth-Cowin N.; Ahmad N.; Barker J.; Bauchmuller K.; Bird S.; Cawthron K.; Harrington K.; Jackson Y.; Kibutu F.; Lenagh B.; Masuko S.; Mills G.H.; Raithatha A.; Wiles M.; Willson J.; Newell H.; Lye A.; Nwafor L.; Jarman C.; Rowland-Jones S.; Foote D.; Cole J.; Thompson R.; Watson J.; Hesseldon L.; Macharia I.; Chetam L.; Ford A.; Birchall K.; Housley K.; Walker S.; Milner L.; Hanratty H.; Trower H.; Phillips P.; Oxspring S.; Donne B.; Jardine C.; Williams D.; Hay A.; Flanagan R.; Hughes G.; Latham S.; McKenna E.; Anderson J.; Hull R.; Rhead K.; Cruz C.; Pattison N.; Charnock R.; McFarland D.; Cosgrove D.; Ahmed A.; Morris A.; Jakkula S.; Nune A.; Brady M.; Dale S.; Dance A.; Gledhill L.; Greig J.; Hanson K.; Holdroyd K.; Home M.; Kelly D.; Kitson R.; Matapure L.; Melia D.; Mellor S.; Nortcliffe T.; Pinnell J.; Robinson M.; Shaw L.; Shaw R.; Thomis L.; Wilson A.; Wood T.; Bayo L.-A.; Merwaha E.; Ishaq T.; Hanley S.; Hibbert M.; Tetla D.; Woodford C.; Durga L.; Kennard-Holden G.; Branney D.; Frankham J.; Pitts S.; Laha S.; Verlander M.; Altabaibeh A.; Alvaro A.; Gilbert K.; Ma L.; Mostoles L.; Parmar C.; Jetha C.; Booker L.; Pratley A.; Adams C.; Agasou A.; Arden T.; Bowes A.; Boyle P.; Beekes M.; Button H.; Capps N.; Carnahan M.; Carter A.; Childs D.; Donaldson D.; Hard K.; Hurford F.; Hussain Y.; Javaid A.; Jones J.; Jose S.; Leigh M.; Martin T.; Millward H.; Motherwell N.; Rikunenko R.; Stickley J.; Summers J.; Ting L.; Tivenan H.; *Tonks L.; *Wilcox R.; Skinner D.; Gaylard J.; Mullan D.; Newman J.; Holland M.; Keenan N.; Lyons M.; Wassall H.; Marsh C.; Mahenthran M.; Carter E.; Kong T.; Blackman H.; Creagh-Brown B.; Donlon S.; Michalak-Glinska N.; Mtuwa S.; Pristopan V.; Salberg A.; Smith E.; Stone S.; Piercy C.; Verula J.; Burda D.; Montaser R.; Harden L.; Mayangao I.; Marriott C.; Bradley P.; Harris C.; Anderson S.; Andrews E.; Hammerton K.; O'Leary R.; Clark M.; Purvis S.; Barber R.; Hewitt C.; Hilldrith A.; Jackson-Lawrence K.; Shepardson S.; Wills M.; Butler S.; Tavares S.; Cunningham A.; Hindale J.; Arif S.; Bean S.; Burt K.; Spivey M.; Demetriou C.; Eckbad C.; Hierons S.; Howie L.; Mitchard S.; Ramos L.; Serrano-Ruiz A.; White K.; Kelly F.; Cristiano D.; Dormand N.; Farzad Z.; Gummadi M.; Liyanage K.; Patel B.; Salmi S.; Sloane G.; Thwaites V.; Varghese M.; Zborowski A.C.; Allan J.; Geary T.; Houston G.; Meikle A.; O'Brien P.; Forsey M.; Kaliappan A.; Riches J.; Vertue M.; Allan E.; Darlington K.; Davies F.; Easton J.; Kumar S.; Lean R.; Menzies D.; Pugh R.; Qiu X.; Davies L.; Williams H.; Scanlon J.; Davies G.; Mackay C.; Lewis J.; Rees S.; Oblak M.; Popescu M.; Thankachen M.; Higham A.; Simpson K.; Craig J.; Baruah R.; Morris S.; Ferguson S.; Shepherd A.; Moore L.S.P.; Vizcaychipi M.P.; de Almeida Martins L.G.; Carungcong J.; Ali I.A.M.; Beaumont K.; Blunt M.; Coton Z.; Curgenven H.; Elsaadany M.; Fernandes K.; Ally S.M.; Rangarajan H.; Sarathy V.; Selvanayagam S.; Vedage D.; White M.; Gill M.; Paul P.; Ratnam V.; Shelton S.; Wynter I.; Carmody S.; Page V.J.; Beith C.M.; Black K.; Clements S.; Morrison A.; Strachan D.; Taylor M.; Clarkson M.; D'Sylva S.; Norman K.; Auld F.; Donnachie J.; Edmond I.; Prentice L.; Runciman N.; Salutous D.; Symon L.; Todd A.; Turner P.; Short A.; Sweeney L.; Murdoch E.; Senaratne D.; Hill M.; Kannan T.; Crawley R.; Crew A.; Cunningham M.; Daniels A.; Harrison L.; Hope S.; Inweregbu K.; Jones S.; Lancaster N.; Matthews J.; Nicholson A.; Wray G.; Langton H.; Prout R.; Watters M.; Novis C.; Barron A.; Collins C.; Kaul S.; Passmore H.; Prendergast C.; Reed A.; Rogers P.; Shokkar R.; Woodruff M.; Middleton H.; Polgar O.; Nolan C.; Mahay K.; Collier D.; Hormis A.; Maynard V.; Graham C.; Walker R.; Knights E.; Price A.; Thomas A.; Thorpe C.; Behan T.; Burnett C.; Hatton J.; Heeney E.; Mitra A.; Newton M.; Pollard R.; Stead R.; Amin V.; Anastasescu E.; Anumakonda V.; Karthik K.; Kausar R.; Reid K.; Smith J.; Imeson-Wood J.; Brown A.; Crickmore V.; Debreceni G.; Wilkins J.; Nicol L.; Reece-Anthony R.; Birt M.; Ghosh A.; Williams E.; Allen L.; Beranova E.; Crisp N.; Deery J.; Hazelton T.; Knight A.; Price C.; Tilbey S.; Turki S.; Turney S.; Cooper J.; Finch C.; Liderth S.; Quinn A.; Waddington N.; Coventry T.; Fowler S.; MacMahon M.; Cowley A.; Highgate J.; Gregory J.; O'Connell S.; Smith T.; Barberis L.; Gopal S.; Harris N.; Lake V.; Metherell S.; Radford E.; Daniel A.; Finn J.; Saha R.; White N.; Donnison P.; Trim F.; Eapen B.; Birch J.; Bough L.; Goodsell J.; Tutton R.; Williams P.; Williams S.; Winter-Goodwin B.; Brickell K.; Smyth M.; Murphy L.; Coetzee S.; Gales A.; Raj M.; Sell C.; Hilltout P.; Evitts J.; Tyler A.; Waldron J.; Beesley K.; Board S.; Kubisz-Pudelko A.; Lewis A.; Perry J.; Pippard L.; Wood D.; Buckley C.; Barry P.; Flint N.; Rekha P.; Hales D.; Bunni L.; Jennings C.; Latif M.; Marshall R.; Subramanian G.; McGuigan P.J.; Wasson C.; Finn S.; Green J.; Collins E.; King B.; Smuts S.; Duffield J.; Smith O.; Mallon L.; Watkins C.; Botfield L.; Butler J.; Dexter C.; Fletcher J.; Garg A.; Kuravi A.; Ranga P.; Virgilio E.; Belagodu Z.; Fuller B.; Gherman A.; Olufuwa O.; Paramsothy R.; Stuart C.; Oakley N.; Kamundi C.; Tyl D.; Collins K.; Silva P.; Taylor J.; King L.; Coates C.; Crowley M.; Wakefield P.; Beadle J.; Johnson L.; Sargeant J.; Anderson M.; Brady A.; Chan R.; Little J.; McIvor S.; Prady H.; Whittle H.; Mathew B.; Attwood B.; Parsons P.; Ward G.; Bremmer P.; Joe W.; Tracy B.; Jim R.; Davies E.; Roche L.; Sathe S.; Dennis C.; McGregor A.; Parris V.; Srikaran S.; Sukha A.; Clarke N.; Whiteside J.; Mascarenhas M.; Donaldson A.; Matheson J.; Barrett F.; O'Hara M.; Okeefe L.; Bradley C.; Eastgate-Jackson C.; Filipe H.; Martin D.; Maharajh A.; Garcia S.M.; Pakou G.; De Neef M.; Dent K.; Horsley E.; Akhtar M.N.; Pearson S.; Potoczna D.; Spencer S.; Clapham M.; Harper R.; Poultney U.; Rice P.; Mutch R.; Armstrong L.; Bates H.; Dooks E.; Farquhar F.; Hairsine B.; McParland C.; Packham S.; Bi R.; Scholefield B.; Ashton L.; George L.; Twiss S.; Wright D.; Chablani M.; Kirkby A.; Netherton K.; Davies K.; O'Brien L.; Omar Z.; Otahal I.; Perkins E.; Lewis T.; Sutherland I.; Burns K.; Chandler B.; Elliott K.; Mallinson J.; Turnbull A.; Gondo P.; Hadebe B.; Kayani A.; Masunda B.; Anderson T.; Hawcutt D.; O'Malley L.; Rad L.; Rogers N.; Saunderson P.; Allison K.S.; Afolabi D.; Whitbread J.; Jones D.; Dore R.; Halkes M.; Mercer P.; Thornton L.; Dawson J.; Garrioch S.; Tolson M.; Aldridge J.; Kapoor R.; Loader D.; Castle K.; Humphreys S.; Tampsett R.; Mackintosh K.; Ayers A.; Harrison W.; North J.; Allibone S.; Genetu R.; Kasipandian V.; Patel A.; Mac A.; Murphy A.; Mahjoob P.; Nazari R.; Worsley L.; Fagan A.; Bemand T.; Black E.; Rosa A.D.; Howle R.; Jhanji S.; Baikady R.R.; Tatham K.C.; Thomas B.; Bell D.; Boyle R.; Douglas K.; Glass L.; Lee E.; Lennon L.; Rattray A.; Taylor A.; Hughes R.A.; Thomas H.; Rees A.; Duskova M.; Phipps J.; Brooks S.; Edwards M.; Quaid S.; Watson E.; Brayne A.; Fisher E.; Hunt J.; Jackson P.; Kaye D.; Love N.; Parkin J.; Tuckey V.; van Koutrik L.; Carter S.; Andrew B.; Findlay L.; Adams K.; Service J.; Williams A.; Cheyne C.; Saunderson A.; Moultrie S.; Odam M.; Hall K.; Mapfunde I.; Willis C.; Lyon A.; Sri-Chandana C.; Scherewode J.; Stephenson L.; Marsh S.; Hardy J.; Houlden H.; Moncur E.; Tariq A.; Tucci A.; Hobrok M.; Loosley R.; McGuinness H.; Tench H.; Wolf-Roberts R.; Irvine V.; Shelley B.; Gorman C.; Gupta A.; Timlick E.; Brady R.; Milligan B.; Bellini A.; Bryant J.; Mayer A.; Pickard A.; Roe N.; Sowter J.; Howlett A.; Fidler K.; Tagliavini E.; Donnelly K.; Shelton J.F.; Shastri A.J.; Ye C.; Weldon C.H.; Filshtein-Sonmez T.; Coker D.; Symons A.; Esparza-Gordillo J.; Aslibekyan S.; Auton A.; Pathak G.A.; Karjalainen J.; Stevens C.; Andrews S.J.; Kanai M.; Cordioli M.; Polimanti R.; Pirinen M.; Harerimana N.; Veerapen K.; Wolford B.; Nguyen H.; Solomonson M.; Liao R.G.; Chwialkowska K.; Trankiem A.; Balaconis M.K.; Hayward C.; Richmond A.; Campbell A.; Morris M.; Fawns-Ritchie C.; Glessner J.T.; Shaw D.M.; Chang X.; Polikowski H.; Petty L.E.; Chen H.-H.; Wanying Z.; Porteous D.J.; Below J.; North K.; McCormick J.B.; Timmers P.H.J.; D'Mellow K.; Kerr S.M.; Niemi M.E.K.; von Hohenstaufen K.A.; Sobh A.; Eltoukhy M.M.; Yassen A.M.; Hegazy M.A.F.; Okasha K.; Eid M.A.; Moahmed H.S.; Shahin D.; El-Sherbiny Y.M.; Elhadidy T.A.; Abd Elghafar M.S.; El-Jawhari J.J.; Mohamed A.A.S.; Elnagdy M.H.; Samir A.; Abdel-Aziz M.; Khafaga W.T.; El-Lawaty W.A.; Torky M.S.; El-shanshory M.R.; Batini C.; Lee P.H.; Shrine N.; Williams A.T.; Tobin M.D.; Guyatt A.L.; John C.; Packer R.J.; Ali A.; Free R.C.; Wang X.; Wain L.V.; Hollox E.J.; Venn L.D.; Bee C.E.; Adams E.L.; Niavarani A.; Sharififard B.; Aliannejad R.; Amirsavadkouhi A.; Naderpour Z.; Tadi H.A.; Aleagha A.E.; Ahmadi S.; Moghaddam S.B.M.; Adamsara A.; Saeedi M.; Abdollahi H.; Hosseini A.; Chariyavilaskul P.; Chamnanphon M.; Suttichet T.B.; Shotelersuk V.; Pongpanich M.; Phokaew C.; Chetruengchai W.; Jantarabenjakul W.; Putchareon O.; Torvorapanit P.; Puthanakit T.; Suchartlikitwong P.; Hirankarn N.; Nilaratanakul V.; Sodsai P.; Brumpton B.M.; Hveem K.; Willer C.; Zhou W.; Rogne T.; Solligard E.; Asvold B.O.; Abedalthagafi M.; Alaamery M.; Alqahtani S.; Barakeh D.; Harthi F.A.; Alsolm E.; Safieh L.A.; Alowayn A.M.; Alqubaishi F.; Mutairi A.A.; Mangul S.; Alshareef A.; Sawaji M.; Almutairi M.; Aljawini N.; Albesher N.; Arabi Y.M.; Mahmoud E.S.; Khattab A.K.; Halawani R.T.; Alahmadey Z.Z.; Albakri J.K.; Felemban W.A.; Suliman B.A.; Hasanato R.; Al-Awdah L.; Alghamdi J.; AlZahrani D.; AlJohani S.; Al-Afghani H.; Alrashed M.; AlDhawi N.; AlBardis H.; Alkwai S.; Alswailm M.; Almalki F.; Albeladi M.; Almohammed I.; Barhoush E.; Albader A.; Massadeh S.; AlMalik A.; Alotaibi S.; Alghamdi B.; Jung J.; Fawzy M.S.; Lee Y.; Magnus P.; Trogstad L.-I.S.; Helgeland O.; Harris J.R.; Mangino M.; Spector T.D.; Duncan E.; Smieszek S.P.; Przychodzen B.P.; Polymeropoulos C.; Polymeropoulos V.; Polymeropoulos M.H.; Fernandez-Cadenas I.; Perez-Tur J.; Llucia-Carol L.; Cullell N.; Muino E.; Carcel-Marquez J.; DeDiego M.L.; Iglesias L.L.; Planas A.M.; Soriano A.; Rico V.; Aguero D.; Bedini J.L.; Lozano F.; Domingo C.; Robles V.; Ruiz-Jaen F.; Marquez L.; Gomez J.; Coto E.; Albaiceta G.M.; Garcia-Clemente M.; Dalmau D.; Arranz M.J.; Dietl B.; Serra-Llovich A.; Soler P.; Colobran R.; Martin-Nalda A.; Martinez A.P.; Bernardo D.; Rojo S.; Fiz-Lopez A.; Arribas E.; de la Cal-Sabater P.; Segura T.; Gonzalez-Villa E.; Serrano-Heras G.; Marti-Fabregas J.; Jimenez-Xarrie E.; Mimbrera A.F.; Masjuan J.; Garcia-Madrona S.; Dominguez-Mayoral A.; Villalonga J.M.; Menendez-Valladares P.; Chasman D.I.; Buring J.E.; Ridker P.M.; Franco G.; Sesso H.D.; Manson J.E.; Glessner J.R.; Hakonarson H.; Medina-Gomez C.; Uitterlinden A.G.; Ikram M.A.; Kristiansson K.; Koskelainen S.; Perola M.; Donner K.; Kivinen K.; Palotie A.; Ripatti S.; Ruotsalainen S.; Kaunisto M.; Nakanishi T.; Butler-Laporte G.; Forgetta V.; Morrison D.R.; Ghosh B.; Laurent L.; Belisle A.; Henry D.; Abdullah T.; Adeleye O.; Mamlouk N.; Kimchi N.; Afrasiabi Z.; Rezk N.; Vulesevic B.; Bouab M.; Guzman C.; Petitjean L.; Tselios C.; Xue X.; Schurr E.; Afilalo J.; Afilalo M.; Oliveira M.; Brenner B.; Lepage P.; Ragoussis J.; Auld D.; Brassard N.; Durand M.; Chasse M.; Kaufmann D.E.; Lathrop G.M.; Mooser V.; Richards J.B.; Li R.; Adra D.; Rahmouni S.; Georges M.; Moutschen M.; Misset B.; Darcis G.; Guiot J.; Guntz J.; Azarzar S.; Gofflot S.; Beguin Y.; Claassen S.; Malaise O.; Huynen P.; Meuris C.; Thys M.; Jacques J.; Leonar P.; Frippiat F.; Giot J.-B.; Sauvage A.-S.; von Frenckell C.; Belhaj Y.; Lambermont B.; Pigazzini S.; Daya M.; Shortt J.; Rafaels N.; Wicks S.J.; Crooks K.; Barnes K.C.; Gignoux C.R.; Chavan S.; Laisk T.; Lall K.; Lepamets M.; Magi R.; Esko T.; Reimann E.; Milani L.; Alavere H.; Metsalu K.; Puusepp M.; Metspalu A.; Naaber P.; Laane E.; Pesukova J.; Peterson P.; Kisand K.; Tabri J.; Allos R.; Hensen K.; Starkopf J.; Ringmets I.; Tamm A.; Kallaste A.; Bochud P.-Y.; Rivolta C.; Bibert S.; Quinodoz M.; Kamdar D.; Boillat N.; Nussle S.G.; Albrich W.; Suh N.; Neofytos D.; Erard V.; Voide C.; de Cid R.; Galvan-Femenia I.; Blay N.; Carreras A.; Cortes B.; Farre X.; Sumoy L.; Moreno V.; Mercader J.M.; Guindo-Martinez M.; Torrents D.; Kogevinas M.; Garcia-Aymerich J.; Castano-Vinyals G.; Dobano C.; Renieri A.; Mari F.; Fallerini C.; Daga S.; Benetti E.; Baldassarri M.; Fava F.; Frullanti E.; Valentino F.; Doddato G.; Giliberti A.; Tita R.; Amitrano S.; Bruttini M.; Croci S.; Meloni I.; Mencarelli M.A.; Rizzo C.L.; Pinto A.M.; Beligni G.; Tommasi A.; Sarno L.D.; Palmieri M.; Carriero M.L.; Alaverdian D.; Busani S.; Bruno R.; Vecchia M.; Belli M.A.; Picchiotti N.; Sanarico M.; Gori M.; Furini S.; Mantovani S.; Ludovisi S.; Mondelli M.U.; Castelli F.; Quiros-Roldan E.; Antoni M.D.; Zanella I.; Vaghi M.; Rusconi S.; Siano M.; Montagnani F.; Emiliozzi A.; Fabbiani M.; Rossetti B.; Bargagli E.; Bergantini L.; D'Alessandro M.; Cameli P.; Bennett D.; Anedda F.; Marcantonio S.; Scolletta S.; Franchi F.; Mazzei M.A.; Guerrini S.; Conticini E.; Cantarini L.; Frediani B.; Tacconi D.; Spertilli C.; Feri M.; Donati A.; Scala R.; Guidelli L.; Spargi G.; Corridi M.; Nencioni C.; Croci L.; Bandini M.; Caldarelli G.P.; Piacentini P.; Desanctis E.; Cappelli S.; Canaccini A.; Verzuri A.; Anemoli V.; Ognibene A.; Pancrazzi A.; Lorubbio M.; Monforte A.D.; Miraglia F.G.; Girardis M.; Venturelli S.; Cossarizza A.; Antinori A.; Vergori A.; Gabrieli A.; Riva A.; Francisci D.; Schiaroli E.; Paciosi F.; Scotton P.G.; Andretta F.; Panese S.; Scaggiante R.; Gatti F.; Parisi S.G.; Baratti S.; Monica M.D.; Piscopo C.; Capasso M.; Russo R.; Andolfo I.; Iolascon A.; Fiorentino G.; Carella M.; Castori M.; Merla G.; Squeo G.M.; Aucella F.; Raggi P.; Marciano C.; Perna R.; Bassetti M.; Biagio A.D.; Sanguinetti M.; Masucci L.; Valente S.; Mandala M.; Giorli A.; Salerni L.; Zucchi P.; Parravicini P.; Menatti E.; Trotta T.; Giannattasio F.; Coiro G.; Lena F.; Coviello D.A.; Mussini C.; Martinelli E.; Mancarella S.; Tavecchia L.; Crotti L.; Gabbi C.; Rizzi M.; Maggiolo F.; Ripamonti D.; Bachetti T.; Rovere M.T.L.; Sarzi-Braga S.; Bussotti M.; Ceri S.; Pinoli P.; Raimondi F.; Biscarini F.; Stella A.; Zguro K.; Capitani K.; Suardi C.; Dei S.; Parati G.; Ravaglia S.; Artuso R.; Botta G.; Di Domenico P.; Rancan I.; Perrella A.; Bianchi F.; Romani D.; Bergomi P.; Catena E.; Colombo R.; Tanfoni M.; Vincenti A.; Ferri C.; Grassi D.; Pessina G.; Tumbarello M.; Di Pietro M.; Sabrina R.; Luchi S.; Barbieri C.; Acquilini D.; Andreucci E.; Segala F.V.; Tiseo G.; Falcone M.; Lista M.; Poscente M.; De Vivo O.; Petrocelli P.; Guarnaccia A.; Baroni S.; Smith A.V.; Boughton A.P.; Li K.W.; LeFaive J.; Annis A.; Chittoor G.; Josyula N.S.; Leader J.B.; Carey D.J.; Gass M.C.; Cantor M.N.; Yadav A.; van Heel D.A.; Hunt K.A.; Mason D.; Huang Q.Q.; Finer S.; Trivedi B.; Griffiths C.J.; Martin H.C.; Wright J.; Trembath R.C.; Soranzo N.; Zhao J.H.; Butterworth A.S.; Danesh J.; Di Angelantonio E.; Franke L.; Boezen M.; Deelen P.; Claringbould A.; Lopera E.; Warmerdam R.; Vonk J.M.; van Blokland I.; Lanting P.; Ori A.P.S.; Zollner S.; Wang J.; Beck A.; Peloso G.; Ho Y.-L.; Sun Y.V.; Huffman J.E.; O'Donnell C.J.; Cho K.; Tsao P.; Gaziano J.M.; Nivard M.; de Geus E.; Bartels M.; Hottenga J.J.; Weiss S.T.; Karlson E.W.; Smoller J.W.; Green R.C.; Feng Y.-C.A.; Mercader J.; Murphy S.N.; Meigs J.B.; Woolley A.E.; Perez E.F.; Rader D.; Li B.; Verma S.S.; Lucas A.; Bradford Y.; Zeberg H.; Frithiof R.; Hultstrom M.; Lipcsey M.; Nkambul L.; Tardif N.; Rooyackers O.; Grip J.; Maricic T.; Karczewski K.J.; Atkinson E.G.; Tsuo K.; Baya N.; Turley P.; Gupta R.; Callier S.; Walters R.K.; Palmer D.S.; Sarma G.; Cheng N.; Lu W.; Bryant S.; Churchhouse C.; Cusick C.; Goldstein J.I.; King D.; Seed C.; Finucane H.; Martin A.R.; Satterstrom F.K.; Wilson D.J.; Armstrong J.; Rudkin J.K.; Band G.; Earle S.G.; Lin S.-K.; Arning N.; Crook D.W.; Wyllie D.H.; O'Connell A.M.; Spencer C.C.A.; Koelling N.; Fowler T.; Pasko D.; Ball C.A.; Hong E.L.; Rand K.; Girshick A.; Guturu H.; Baltzell A.H.; Roberts G.; Park D.; Coignet M.; McCurdy S.; Knight S.; Partha R.; Rhead B.; Zhang M.; Berkowitz N.; Gaddis M.; Noto K.; Ruiz L.; Pavlovic M.; Sloofman L.G.; Charney A.W.; Beckmann N.D.; Schadt E.E.; Jordan D.M.; Thompson R.C.; Gettler K.; Abul-Husn N.S.; Ascolillo S.; Buxbaum J.D.; Chaudhary K.; Cho J.H.; Itan Y.; Kenny E.E.; Belbin G.M.; Sealfon S.C.; Sebra R.P.; Salib I.; Collins B.L.; Levy T.; Britvan B.; Keller K.; Tang L.; Peruggia M.; Hiester L.L.; Niblo K.; Aksentijevich A.; Labkowsky A.; Karp A.; Zlatopolsky M.; Preuss M.; Loos R.J.F.; Nadkarni G.N.; Do R.; Hoggart C.; Choi S.; Underwood S.J.; O'Reilly P.; Huckins L.M.; Zyndorf M.; Daly M.J.; Neale B.M.; Ganna A.

Citation:
Nature, 2022. Vol 607(7917) (pp 97-103)

Abstract:
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

Link to full-text [open access - no password required]

Altmetrics:

Results of an audit of the Peristomal Body Profile Assessment Tool (2022)

Type of publication:
Journal article

Author(s):
*Nicola Tonks Natasha Rolls, Kimberly Bain, Paul Russell-Roberts and Mark Bain

Citation:
British Journal of Nursing, December 2022, Vol 31, No 22, S4-S12 (Stoma Care Supplement)

Abstract:
Background: Leakage is the number one concern for people with an ostomy. The 2019 Ostomy Life Study, a global study of more than 5000 ostomates, showed that 92% of people living with a stoma worry about leakage. Getting the right stoma appliance for each patient is key to increasing patient quality of life. Aim: The study was designed to assess the use of the PeristomalBody Profile Assessment Tool in helping choose the most appropriate stoma products for a given patient, decreasing incidents of leakage and peristomal skin complications. Methods: A multi-centre (33 sites, 147 patients) low-interventional clinical investigation was conducted in which the use of the Peristomal BodyProfile Assessment Tool was evaluated as a tool to reduce incidents of leakage, increase peristomal skin health and increase patient quality of life. A focus group of randomised participating clinicians (n=16) was held to explore the audit results. Results: The assessment tool most often took between 2 and 5 minutes to complete. It supported clinicians in selecting the right appliance for each patient, avoiding leakages and preventing associated peristomal skin complications. The assessment tool helped improve the accuracy and quality of documentation in the patients’ medical/nursing notes, increasing the quality and continuity of care. Participants reported that using the assessment tool helped reduce care costs by reducing the need for product changes, supporting product usage and return patient visits. Conclusion: Use of the Peristomal Body Profile Assessment Tool helped clinicians choose the most appropriate stoma appliance the first time, resulting in patients having healthier peristomal skin, fewer leakages, more confidence in their stoma appliance and a higher quality of life.

Link to full-text [NHS OpenAthens account required]